Environmental tobacco smoke (ETS) is a mixture of aged and diluted sidestream smoke (SS) arising from the end of a lit cigarette between puffs or from mainstream cigarette smoke (MS) exhaled by smokers. While the adverse health effects of smoking are well documented, controversy persists with regard to the health hazards of ETS on human adults. However, evidence is increasing that children exposed prenatally (in utero) and postnatally to ETS are at higher risk of developing respiratory tract infections. Data from animal models indicate that SS, in practical environmental concentrations, does not cause significant physiological or histopathological changes in the lung. Thus, reasons for the higher susceptibility of SS-exposed children to infections is not clear. To our knowledge, none of the studies to date has evaluated the immunocompetence of animals exposed prenatally/postnatally to SS. The investigators have demonstrated that chronic exposure of mice or rats to cigarette smoke/nicotine induces T cell tolerance and a significant loss of the antibody-forming cell (AFC) response in the absence of detectable histopathologial changes. Moreover, their preliminary experiments suggest that, following influenza infection, viral titers in the lungs of nicotine-treated mice are several fold higher than in control animals. The aim of this proposal is to test the hypothesis that pre-and/or postnatal exposure to SS, in concentrations observed in areas where smokers are present, will adversely affect the immune response and increase the susceptibility to pulmonary infections. Prospective mothers from SWR mice will be exposed to SS (120 ug/m3) or filtered air (FA) 2wk before and during pregnancy. After birth, each group will be divided into representing the following prenatal/postnatal treatments: (FA/FA; FA/SS; SS/FA; SS/SS). Exposures of these groups will be continued postnatally for 6 wk. These animals will be evaluated for immunopathology, the AFC response to T cell-dependent and T-cell independent antigens, antigen presentation, cytokine production, fever response to turpentine-induced sterile abscess, and resistance to influenza virus infection. Results from these experiments should help to evaluate the possibility that pre-and/or postnatal exposure to SS impairs the immune system, and help to design experiments to determine the mechanism of increased pulmonary infections in children of smokers.